Objective:Negative self-concept is characteristic of anorexia nervosa (AN), but the neural proces... more Objective:Negative self-concept is characteristic of anorexia nervosa (AN), but the neural processes mediating this component of AN are unknown. These studies investigated how valence and social perspectives impact neural processing in both adults and adolescents with anorexia nervosa (AN).Method:In an fMRI task, participants evaluated positive and negative adjectives from three social perspectives. Two studies were completed, one in 59 women (healthy, with AN, recovered from AN) and one in 42 adolescents (healthy, with AN). Neural regions of interest (ROIs) related to valence were identified and activations compared across groups and social perspectives.Results:Behaviorally, both adult and adolescent cohorts with AN were less positive during self-evaluations. In the adult study, neural differences related to clinical group and condition were observed in ROIs more responsive to positive social stimuli (medial prefrontal cortex, precuneus, left temporoparietal junction) but not in ROIs more responsive to negative social stimuli. No neural differences in relation to clinical group were observed in the adolescents.Conclusions:Behavioral differences related to negative self-concept are present in both adolescents and adults with AN, and neural differences, selective for positive social stimuli, were also observed in adults. AN may interfere with neurodevelopmental processes involved in positive self-concept.
In anorexia nervosa, problems with social relationships contribute to illness, and improvements i... more In anorexia nervosa, problems with social relationships contribute to illness, and improvements in social support are associated with recovery. Using the multiround trust game and 3T MRI, we compare neural responses in a social relationship in three groups of women: women with anorexia nervosa, women in long-term weight recovery from anorexia nervosa, and healthy comparison women. Surrogate markers related to social signals in the game were computed each round to assess whether the relationship was improving (benevolence) or deteriorating (malevolence) for each subject. Compared with healthy women, neural responses to benevolence were diminished in the precuneus and right angular gyrus in both currently-ill and weight-recovered subjects with anorexia, but neural responses to malevolence differed in the left fusiform only in currently-ill subjects. Next, using a whole-brain regression, we identified an office assessment, the positive personalizing bias, that was inversely correlated with neural activity in the occipital lobe, the precuneus and posterior cingulate, the bilateral temporoparietal junctions, and dorsal anterior cingulate, during benevolence for all groups of subjects. The positive personalizing bias is a self-report measure that assesses the degree with which a person attributes positive experiences to other people. These data suggest that problems in perceiving kindness may be a consistent trait related to the development of anorexia nervosa, whereas recognizing malevolence may be related to recovery. Future work on social brain function, in both healthy and psychiatric populations, should consider positive personalizing biases as a possible marker of neural differences related to kindness perception.
ObjectiveImproved understanding of adolescent eating disorders (EDs), including identification an... more ObjectiveImproved understanding of adolescent eating disorders (EDs), including identification and refinement of treatment and recovery targets, may help improve clinical outcomes. Interpersonal function is a proposed risk and maintenance factor that may be particularly relevant given the significance of adolescence for both psychosocial development and ED onset. This study examined self‐referential thinking in adolescents with EDs compared to healthy adolescents.MethodTwenty‐nine adolescents with EDs and 31 healthy controls completed a self‐report measure of interpersonal attributions as well as a verbal appraisal task that required conducting direct and indirect evaluations about oneself and direct evaluations about others.ResultsThe ED group had a more negative self‐attribution bias than the control group (p = 0.006) even when controlling for depression severity. Additionally, the ED group exhibited less positive direct self (p < 0.001), direct social (p = 0.015), and social reflected self‐appraisals (p = 0.011) than the healthy cohort. After including depression as a covariate in the verbal appraisal model, the model was no longer significant, suggesting group differences related to social appraisals may be mediated by depression.ConclusionsAdolescents with EDs have more negative interpersonal beliefs than comparison adolescents. Future studies are needed to determine how the constructs identified here relate to clinical course.
We write in regard to the recent publication "Prevalence and Correlates of DSM-5-Defined Eating D... more We write in regard to the recent publication "Prevalence and Correlates of DSM-5-Defined Eating Disorders in a Nationally Representative Sample of U.S. Adults" (1). We previously obtained the same dataset from the National Epidemiologic Survey on Alcohol and Related Conditions and became concerned about the ability of this structured phone interview (Alcohol Use Disorder and Associated Disabilities Interview Schedule-5) to assess eating disorders.
Journal of behavioral and cognitive therapy, Mar 1, 2021
Eating disorders (EDs) are characterized by altered eating behaviors and valuation of self-image,... more Eating disorders (EDs) are characterized by altered eating behaviors and valuation of self-image, as well as difficulty establishing supportive social relationships. This pilot study evaluated feasibility, acceptability, and clinical responses to a novel and brief group-therapy intervention for EDs, the Self-Blame and Perspective-Taking Intervention (SBPI). The SBPI consisted of four sessions of experiential art therapy activities in conjunction with psychoeducation targeting interpersonal attributions and mentalization. Twenty-four outpatient, treatment-seeking women with EDs participated in the SBPI, with 87.5% completing the intervention and 94% rating their participation positively. ED symptoms, depression, anxiety, self-attribution bias, and self-esteem were assessed before (T1) and after participation (N = 20 at T2; N = 18 at T3). Separate repeated measures MANOVAs were performed to assess these clinical and self-concept variables. Relative to baseline, participants demonstrated significant improvements in two all self-concept measures: self-attribution bias, trait self-esteem and state self-esteem at T2. ED, depression, and anxiety symptoms were significantly decreased at both T2 (1-4 weeks post) and T3 (3-5 months post). The SBPI altered self-concept targets acutely and led to sustained clinical improvements. Future work is needed to evaluate how self-concept and social constructs are related to clinical symptom expression in EDs.
Objective-To determine if an interpersonal attribution bias associated with self-perception, the ... more Objective-To determine if an interpersonal attribution bias associated with self-perception, the externalizing bias, was related to neural activations during mentalization. Methods-A functional magnetic resonance imaging task involving verbal appraisals measured neural activations when thinking about oneself and others in 59 adults, including healthy women as well as women with and recovered from anorexia nervosa. Whole-brain regressions correlated brain function during mentalization with the externalizing bias measured using the Internal, Personal, and Situational Attributions Questionnaire. Results-Women with anorexia nervosa had a lower externalizing bias, demonstrating a tendency to self-attribute more negative than positive social interactions, unlike the other groups. The externalizing bias was correlated with activation of the left inferior frontal gyrus and posterior insula, when comparing thinking about others evaluating oneself with direct self-evaluation. Discussion-Externalizing biases may provide an office-based assay reflecting neurocognitive disturbances in social self-perception that are common during anorexia nervosa.
Anorexia nervosa (AN) is an illness that frequently begins during adolescence and involves weight... more Anorexia nervosa (AN) is an illness that frequently begins during adolescence and involves weight loss. Two groups of adolescent girls (AN-A, weight-recovered following AN) and (HC-A, healthy comparison) completed a functional magnetic resonance imaging task involving social evaluations, allowing comparison of neural activations during self-evaluations, friend-evaluations, and perspective-taking self-evaluations. Although the two groups were not different in their wholebrain activations, anxiety and body shape concerns were correlated with neural activity in a priori regions of interest. A cluster in medial prefrontal cortex and the dorsal anterior cingulate correlated with the body shape questionnaire; subjects with more body shape concerns used this area less during self than friend evaluations. A cluster in medial prefrontal cortex and the cingulate also correlated with anxiety such that more anxiety was associated with engagement when disagreeing rather than agreeing with social terms during self-evaluations. This data suggests that differences in the utilization of frontal brain regions during social evaluations may contribute to both anxiety and body shape concerns in adolescents with AN. Clinical follow-up was obtained, allowing exploration of whether brain function early in course of disease relates to illness trajectory. The adolescents successful in recovery used the posterior cingulate and precuneus more for friend than self evaluations than the adolescents that remained ill, suggesting that neural differences related to social evaluations may provide clinical predictive value. Utilization of both MPFC and the precuneus during social and self evaluations may be a key biological component for achieving sustained weight-recovery in adolescents with AN.
Objective-To identify clinical or cognitive measures either predictive of illness trajectory or a... more Objective-To identify clinical or cognitive measures either predictive of illness trajectory or altered with sustained weight-recovery in adult women with anorexia nervosa. Methods-Participants were recruited from prior studies of women with anorexia nervosa (AN-C) and in weight-recovery following anorexia nervosa (AN-WR). Participants completed a neuropsychological battery at baseline and clinical assessments at both baseline and follow up. Groups based on clinical outcome (continued eating disorder, AN-CC; newly in recovery, AN-CR; sustained weight-recovery, AN-WR) were compared using one-way ANOVAs with Bonferronicorrected post hoc comparisons. Results-AN-CC had poorer neuropsychological function and self-competence at baseline than AN-CR. AN-CR showed changes in depression and externalizing bias, a measure of self-related attributions. AN-WR differed from both AN-CC and AN-CR at baseline in externalizing bias, but only from AN-CC at outcome. Discussion-Neuropsychological function when recently ill may be a prognostic factor, while externalizing bias may provide a clinical target for recovery.
Social Cognitive and Affective Neuroscience, Sep 29, 2012
Anorexia nervosa (AN) patients exhibit a disparity in their actual physical identity and their co... more Anorexia nervosa (AN) patients exhibit a disparity in their actual physical identity and their cognitive understanding of their physical identity. Functional magnetic resonance imaging (fMRI) tasks have contributed to understanding the neural circuitry involved in processing identity in healthy individuals. We hypothesized that women recovering from AN would show altered neural responses while thinking about their identity compared with healthy control women. We compared brain activation using fMRI in 18 women recovering from anorexia (RAN) and 18 healthy control women (CON) using two identity-appraisal tasks. These neuroimaging tasks were focused on separable components of identity: one consisted of adjectives related to social activities and the other consisted of physical descriptive phrases about ones appearance. Both tasks consisted of reading and responding to statements with three different perspectives: Self, Friend and Reflected. In the comparisons of the RAN and CON subjects, we observed differences in fMRI activation relating to self-knowledge (I am, I look) and perspective-taking (I believe, Friend believes) in the precuneus, two areas of the dorsal anterior cingulate, and the left middle frontal gyrus. These data suggest that further exploration of neural components related to identity may improve our understanding of the pathology of AN.
Eating disorders are complex and serious psychiatric illnesses whose etiology includes psychologi... more Eating disorders are complex and serious psychiatric illnesses whose etiology includes psychological, biological, and social factors. Treatment of eating disorders is challenging as there are few evidence-based treatments and limited understanding of the mechanisms that result in sustained recovery. In the last 20 years, we have begun to identify neural pathways that are altered in eating disorders. Consideration of how these pathways may contribute to an eating disorder can provide an understanding of expected responses to treatments. Eating disorder behaviors include restrictive eating, compulsive overeating, and purging behaviors after eating. Eating disorders are associated with changes in many neural systems. In this targeted review, we focus on three cognitive processes associated with neurocircuitry differences in subjects with eating disorders such as reward, decision-making, and social behavior. We briefly examine how each of these systems function in healthy people, using Neurosynth meta-analysis to identify key regions commonly implicated in these circuits. We review the evidence for disruptions of these regions and systems in eating disorders. Finally, we describe psychiatric and psychological treatments that are likely to function by impacting these regions.
Phase-Contrast MRI (PC-MRI) is a noninvasive technique to measure blood flow. In particular, glob... more Phase-Contrast MRI (PC-MRI) is a noninvasive technique to measure blood flow. In particular, global but highly quantitative cerebral blood flow (CBF) measurement using PC-MRI complements several other CBF mapping methods such as arterial spin labeling and dynamic susceptibility contrast MRI by providing a calibration factor. The ability to estimate blood supply in physiological units also lays a foundation for assessment of brain metabolic rate. However, a major obstacle before wider applications of this method is that the slice positioning of the scan, ideally placed perpendicular to the feeding arteries, requires considerable expertise and can present a burden to the operator. In the present work, we proposed that the majority of PC-MRI scans can be positioned using an automatic algorithm, leaving only a small fraction of arteries requiring manual positioning. We implemented and evaluated an algorithm for this purpose based on feature extraction of a survey angiogram, which is of minimal operator dependence. In a comparative test-retest study with 7 subjects, the blood flow measurement using this algorithm showed an inter-session coefficient of variation (CoV) of 4:07+3:03%. The Bland-Altman method showed that the automatic method differs from the manual method by between {8% and 11%, for 95% of the CBF measurements. This is comparable to the variance in CBF measurement using manually-positioned PC MRI alone. In a further application of this algorithm to 157 consecutive subjects from typical clinical cohorts, the algorithm provided successful positioning in 89.7% of the arteries. In 79.6% of the subjects, all four arteries could be planned using the algorithm. Chi-square tests of independence showed that the success rate was not dependent on the age or gender, but the patients showed a trend of lower success rate (p = 0.14) compared to healthy controls. In conclusion, this automatic positioning algorithm could improve the application of PC-MRI in CBF quantification.
Eating disorders develop through a combination of genetic vulnerability and environmental stress,... more Eating disorders develop through a combination of genetic vulnerability and environmental stress, however the genetic basis of this risk is unknown. Methods To understand the genetic basis of this risk, we performed whole exome sequencing on 93 unrelated individuals with eating disorders (38 restricted-eating and 55 binge-eating) to identify novel damaging variants. Candidate genes with an excessive burden of predicted damaging variants were then prioritized based upon an unbiased, data-driven bioinformatic analysis. One top candidate pathway was empirically tested for therapeutic potential in a mouse model of binge-like eating. Results An excessive burden of novel damaging variants was identified in 186 genes in the restricted-eating group and 245 genes in the binge-eating group. This list is significantly enriched (OR = 4.6, p<0.0001) for genes involved in neuropeptide/neurotrophic pathways implicated in appetite regulation, including neurotensin-, glucagon-like peptide 1-and BDNF-signaling. Administration of the glucagon-like peptide 1 receptor agonist exendin-4 significantly reduced food intake in a mouse model of 'binge-like' eating. Conclusions These findings implicate ultra-rare and novel damaging variants in neuropeptide/neurotropic factor signaling pathways in the development of eating disorder behaviors and identify glucagon-like peptide 1-receptor agonists as a potential treatment for binge eating.
Anorexia nervosa and bulimia nervosa are common and severe eating disorders (EDs) of unknown etio... more Anorexia nervosa and bulimia nervosa are common and severe eating disorders (EDs) of unknown etiology. Although genetic factors have been implicated in the psychopathology of EDs, a clear biological pathway has not been delineated. DNA from two large families affected by EDs was collected, and mutations segregating with illness were identified by whole-genome sequencing following linkage mapping or by whole-exome sequencing. In the first family, analysis of twenty members across three generations identified a rare missense mutation in the estrogen-related receptor α (ESRRA) gene that segregated with illness. In the second family, analysis of eight members across four generations identified a missense mutation in the histone deacetylase 4 (HDAC4) gene that segregated with illness. ESRRA and HDAC4 were determined to interact both in vitro in HeLa cells and in vivo in mouse cortex. Transcriptional analysis revealed that HDAC4 potently represses the expression of known ESRRA-induced target genes. Biochemical analysis of candidate mutations revealed that the identified ESRRA mutation decreased its transcriptional activity, while the HDAC4 mutation increased transcriptional repression of ESRRA. Our findings suggest that mutations that result in decreased ESRRA activity increase the risk of developing EDs.
Instead, all signals appear to be multiplicatively scaled by attention. Houston, Texas 77030 The ... more Instead, all signals appear to be multiplicatively scaled by attention. Houston, Texas 77030 The effects of attention on the second aspect of neuronal responses, the noise, have not previously been studied. Spike counts of the responses of neocortical Summary neurons to stimuli that are present for several hundred milliseconds are characteristically variable (Tolhurst et To determine the physiological mechanisms underlying the enhancement of performance by attention, we al., 1981; Tomko and Crapper, 1984; Snowden et al., 1992), far more so than the responses of some peripheral examined how attention affects the ability of isolated neurons to discriminate orientation by investigating neurons (e.g., Matthews and Stein, 1969; Whitsel et al., 1977). The source of the variability is unknown. It may the reliability of responses with and without attention. Recording from 262 neurons in cortical area V4 while result from several sources, including synaptic processes, cyclical changes resulting from slow-wave ac-two rhesus macaques did a delayed match-to-sample task with oriented stimuli, we found that attention did tivity in the brain, or changes in the response characteristics of individual neurons (Tomko and Crapper, 1984; not produce detectable changes in the variability of neuronal responses but did improve the orientation Softky and Koch, 1993; Shadlen and Newsome, 1995, 1998). Some studies have suggested that lower variance discriminability of the neurons. We also found that attention did not change the relationship between is found in alert animals compared to anesthetized animals, although the effects are typically small (Vogels et burst rate and response rate. Our results are consistent with the idea that attention selects groups of neu-al., 1989; Snowden et al., 1992). The variability of responses depends in a characteris-rons for a multiplicative enhancement in response strength. tic way on response magnitude. The variance of spike counts is typically proportional to the mean number of spikes produced by a stimulus (Henry et al., 1973; Heg
We examined how attention affected the orientation tuning of 262 isolated neurons in extrastriate... more We examined how attention affected the orientation tuning of 262 isolated neurons in extrastriate area V4 and 135 neurons in area V1 of two rhesus monkeys. The animals were trained to perform a delayed match-to-sample task in which oriented stimuli were presented in the receptive field of the neuron being recorded. On some trials the animals were instructed to pay attention to those stimuli, and on other trials they were instructed to pay attention to other stimuli outside the receptive field. In this way, orientation-tuning curves could be constructed from neuronal responses collected in two behavioral states: one in which those stimuli were attended by the animal and one in which those stimuli were ignored by the animal. We fit Gaussians to the neuronal responses to twelve different orientations for each behavioral state. Although attention enhanced the responses of V4 neurons (median 26% increase) and V1 neurons (median 8% increase), selectivity, as measured by the width of its orientation-tuning curve, was not systematically altered by attention. The effects of attention were consistent with a multiplicative scaling of the driven response to all orientations. We also found that attention did not cause systematic changes in the undriven activity of the neurons.
Anorexia nervosa (AN) patients have been found to have problems in social cognition, including th... more Anorexia nervosa (AN) patients have been found to have problems in social cognition, including the process of thinking about other people&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s thoughts and feelings, often referred to as Theory of Mind (ToM). We examined neural correlates relating to thinking about social relationships in 17 women in recovery from anorexia (RAN) and 17 healthy women (CON) using a functional magnetic resonance imaging (fMRI) task. The task consisted of short videos of moving shapes that subjects viewed either in the context of performing a social decision related to how the shapes interacted: &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;People: All friends?&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; or in the context of performing a visuospatial task related to how the shapes moved after bumping into each other: &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Bumper cars: Same weight?&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;. The RAN participants showed reduced activation in the social cognition network, with the most robust differences in the right temporoparietal junction (RTPJ). There were no significant differences between the CON and RAN groups in regions more active during the visuospatial task. These neural correlates show differences in the processing of social knowledge in RAN subjects suggesting that biological impairments in social cognition may contribute to pathology in AN.
Attention is the mechanism with which we select specific aspects of our environment for processin... more Attention is the mechanism with which we select specific aspects of our environment for processing. Psychological experiments have shown that attention can be directed to a spatial location or to a particular object. Electrophysiological studies in trained macaque monkeys have found that attention can strengthen the responses of neurons in cortical area V4. Some of these studies have attributed these effects to spatial attention, whereas others have suggested that feature-directed attention may modulate the neuronal response. Here we report that neuronal correlates for both spatial and feature-directed attention exist in individual neurons in area V4 of behaving rhesus monkeys.
Objective:Negative self-concept is characteristic of anorexia nervosa (AN), but the neural proces... more Objective:Negative self-concept is characteristic of anorexia nervosa (AN), but the neural processes mediating this component of AN are unknown. These studies investigated how valence and social perspectives impact neural processing in both adults and adolescents with anorexia nervosa (AN).Method:In an fMRI task, participants evaluated positive and negative adjectives from three social perspectives. Two studies were completed, one in 59 women (healthy, with AN, recovered from AN) and one in 42 adolescents (healthy, with AN). Neural regions of interest (ROIs) related to valence were identified and activations compared across groups and social perspectives.Results:Behaviorally, both adult and adolescent cohorts with AN were less positive during self-evaluations. In the adult study, neural differences related to clinical group and condition were observed in ROIs more responsive to positive social stimuli (medial prefrontal cortex, precuneus, left temporoparietal junction) but not in ROIs more responsive to negative social stimuli. No neural differences in relation to clinical group were observed in the adolescents.Conclusions:Behavioral differences related to negative self-concept are present in both adolescents and adults with AN, and neural differences, selective for positive social stimuli, were also observed in adults. AN may interfere with neurodevelopmental processes involved in positive self-concept.
In anorexia nervosa, problems with social relationships contribute to illness, and improvements i... more In anorexia nervosa, problems with social relationships contribute to illness, and improvements in social support are associated with recovery. Using the multiround trust game and 3T MRI, we compare neural responses in a social relationship in three groups of women: women with anorexia nervosa, women in long-term weight recovery from anorexia nervosa, and healthy comparison women. Surrogate markers related to social signals in the game were computed each round to assess whether the relationship was improving (benevolence) or deteriorating (malevolence) for each subject. Compared with healthy women, neural responses to benevolence were diminished in the precuneus and right angular gyrus in both currently-ill and weight-recovered subjects with anorexia, but neural responses to malevolence differed in the left fusiform only in currently-ill subjects. Next, using a whole-brain regression, we identified an office assessment, the positive personalizing bias, that was inversely correlated with neural activity in the occipital lobe, the precuneus and posterior cingulate, the bilateral temporoparietal junctions, and dorsal anterior cingulate, during benevolence for all groups of subjects. The positive personalizing bias is a self-report measure that assesses the degree with which a person attributes positive experiences to other people. These data suggest that problems in perceiving kindness may be a consistent trait related to the development of anorexia nervosa, whereas recognizing malevolence may be related to recovery. Future work on social brain function, in both healthy and psychiatric populations, should consider positive personalizing biases as a possible marker of neural differences related to kindness perception.
ObjectiveImproved understanding of adolescent eating disorders (EDs), including identification an... more ObjectiveImproved understanding of adolescent eating disorders (EDs), including identification and refinement of treatment and recovery targets, may help improve clinical outcomes. Interpersonal function is a proposed risk and maintenance factor that may be particularly relevant given the significance of adolescence for both psychosocial development and ED onset. This study examined self‐referential thinking in adolescents with EDs compared to healthy adolescents.MethodTwenty‐nine adolescents with EDs and 31 healthy controls completed a self‐report measure of interpersonal attributions as well as a verbal appraisal task that required conducting direct and indirect evaluations about oneself and direct evaluations about others.ResultsThe ED group had a more negative self‐attribution bias than the control group (p = 0.006) even when controlling for depression severity. Additionally, the ED group exhibited less positive direct self (p &lt; 0.001), direct social (p = 0.015), and social reflected self‐appraisals (p = 0.011) than the healthy cohort. After including depression as a covariate in the verbal appraisal model, the model was no longer significant, suggesting group differences related to social appraisals may be mediated by depression.ConclusionsAdolescents with EDs have more negative interpersonal beliefs than comparison adolescents. Future studies are needed to determine how the constructs identified here relate to clinical course.
We write in regard to the recent publication "Prevalence and Correlates of DSM-5-Defined Eating D... more We write in regard to the recent publication "Prevalence and Correlates of DSM-5-Defined Eating Disorders in a Nationally Representative Sample of U.S. Adults" (1). We previously obtained the same dataset from the National Epidemiologic Survey on Alcohol and Related Conditions and became concerned about the ability of this structured phone interview (Alcohol Use Disorder and Associated Disabilities Interview Schedule-5) to assess eating disorders.
Journal of behavioral and cognitive therapy, Mar 1, 2021
Eating disorders (EDs) are characterized by altered eating behaviors and valuation of self-image,... more Eating disorders (EDs) are characterized by altered eating behaviors and valuation of self-image, as well as difficulty establishing supportive social relationships. This pilot study evaluated feasibility, acceptability, and clinical responses to a novel and brief group-therapy intervention for EDs, the Self-Blame and Perspective-Taking Intervention (SBPI). The SBPI consisted of four sessions of experiential art therapy activities in conjunction with psychoeducation targeting interpersonal attributions and mentalization. Twenty-four outpatient, treatment-seeking women with EDs participated in the SBPI, with 87.5% completing the intervention and 94% rating their participation positively. ED symptoms, depression, anxiety, self-attribution bias, and self-esteem were assessed before (T1) and after participation (N = 20 at T2; N = 18 at T3). Separate repeated measures MANOVAs were performed to assess these clinical and self-concept variables. Relative to baseline, participants demonstrated significant improvements in two all self-concept measures: self-attribution bias, trait self-esteem and state self-esteem at T2. ED, depression, and anxiety symptoms were significantly decreased at both T2 (1-4 weeks post) and T3 (3-5 months post). The SBPI altered self-concept targets acutely and led to sustained clinical improvements. Future work is needed to evaluate how self-concept and social constructs are related to clinical symptom expression in EDs.
Objective-To determine if an interpersonal attribution bias associated with self-perception, the ... more Objective-To determine if an interpersonal attribution bias associated with self-perception, the externalizing bias, was related to neural activations during mentalization. Methods-A functional magnetic resonance imaging task involving verbal appraisals measured neural activations when thinking about oneself and others in 59 adults, including healthy women as well as women with and recovered from anorexia nervosa. Whole-brain regressions correlated brain function during mentalization with the externalizing bias measured using the Internal, Personal, and Situational Attributions Questionnaire. Results-Women with anorexia nervosa had a lower externalizing bias, demonstrating a tendency to self-attribute more negative than positive social interactions, unlike the other groups. The externalizing bias was correlated with activation of the left inferior frontal gyrus and posterior insula, when comparing thinking about others evaluating oneself with direct self-evaluation. Discussion-Externalizing biases may provide an office-based assay reflecting neurocognitive disturbances in social self-perception that are common during anorexia nervosa.
Anorexia nervosa (AN) is an illness that frequently begins during adolescence and involves weight... more Anorexia nervosa (AN) is an illness that frequently begins during adolescence and involves weight loss. Two groups of adolescent girls (AN-A, weight-recovered following AN) and (HC-A, healthy comparison) completed a functional magnetic resonance imaging task involving social evaluations, allowing comparison of neural activations during self-evaluations, friend-evaluations, and perspective-taking self-evaluations. Although the two groups were not different in their wholebrain activations, anxiety and body shape concerns were correlated with neural activity in a priori regions of interest. A cluster in medial prefrontal cortex and the dorsal anterior cingulate correlated with the body shape questionnaire; subjects with more body shape concerns used this area less during self than friend evaluations. A cluster in medial prefrontal cortex and the cingulate also correlated with anxiety such that more anxiety was associated with engagement when disagreeing rather than agreeing with social terms during self-evaluations. This data suggests that differences in the utilization of frontal brain regions during social evaluations may contribute to both anxiety and body shape concerns in adolescents with AN. Clinical follow-up was obtained, allowing exploration of whether brain function early in course of disease relates to illness trajectory. The adolescents successful in recovery used the posterior cingulate and precuneus more for friend than self evaluations than the adolescents that remained ill, suggesting that neural differences related to social evaluations may provide clinical predictive value. Utilization of both MPFC and the precuneus during social and self evaluations may be a key biological component for achieving sustained weight-recovery in adolescents with AN.
Objective-To identify clinical or cognitive measures either predictive of illness trajectory or a... more Objective-To identify clinical or cognitive measures either predictive of illness trajectory or altered with sustained weight-recovery in adult women with anorexia nervosa. Methods-Participants were recruited from prior studies of women with anorexia nervosa (AN-C) and in weight-recovery following anorexia nervosa (AN-WR). Participants completed a neuropsychological battery at baseline and clinical assessments at both baseline and follow up. Groups based on clinical outcome (continued eating disorder, AN-CC; newly in recovery, AN-CR; sustained weight-recovery, AN-WR) were compared using one-way ANOVAs with Bonferronicorrected post hoc comparisons. Results-AN-CC had poorer neuropsychological function and self-competence at baseline than AN-CR. AN-CR showed changes in depression and externalizing bias, a measure of self-related attributions. AN-WR differed from both AN-CC and AN-CR at baseline in externalizing bias, but only from AN-CC at outcome. Discussion-Neuropsychological function when recently ill may be a prognostic factor, while externalizing bias may provide a clinical target for recovery.
Social Cognitive and Affective Neuroscience, Sep 29, 2012
Anorexia nervosa (AN) patients exhibit a disparity in their actual physical identity and their co... more Anorexia nervosa (AN) patients exhibit a disparity in their actual physical identity and their cognitive understanding of their physical identity. Functional magnetic resonance imaging (fMRI) tasks have contributed to understanding the neural circuitry involved in processing identity in healthy individuals. We hypothesized that women recovering from AN would show altered neural responses while thinking about their identity compared with healthy control women. We compared brain activation using fMRI in 18 women recovering from anorexia (RAN) and 18 healthy control women (CON) using two identity-appraisal tasks. These neuroimaging tasks were focused on separable components of identity: one consisted of adjectives related to social activities and the other consisted of physical descriptive phrases about ones appearance. Both tasks consisted of reading and responding to statements with three different perspectives: Self, Friend and Reflected. In the comparisons of the RAN and CON subjects, we observed differences in fMRI activation relating to self-knowledge (I am, I look) and perspective-taking (I believe, Friend believes) in the precuneus, two areas of the dorsal anterior cingulate, and the left middle frontal gyrus. These data suggest that further exploration of neural components related to identity may improve our understanding of the pathology of AN.
Eating disorders are complex and serious psychiatric illnesses whose etiology includes psychologi... more Eating disorders are complex and serious psychiatric illnesses whose etiology includes psychological, biological, and social factors. Treatment of eating disorders is challenging as there are few evidence-based treatments and limited understanding of the mechanisms that result in sustained recovery. In the last 20 years, we have begun to identify neural pathways that are altered in eating disorders. Consideration of how these pathways may contribute to an eating disorder can provide an understanding of expected responses to treatments. Eating disorder behaviors include restrictive eating, compulsive overeating, and purging behaviors after eating. Eating disorders are associated with changes in many neural systems. In this targeted review, we focus on three cognitive processes associated with neurocircuitry differences in subjects with eating disorders such as reward, decision-making, and social behavior. We briefly examine how each of these systems function in healthy people, using Neurosynth meta-analysis to identify key regions commonly implicated in these circuits. We review the evidence for disruptions of these regions and systems in eating disorders. Finally, we describe psychiatric and psychological treatments that are likely to function by impacting these regions.
Phase-Contrast MRI (PC-MRI) is a noninvasive technique to measure blood flow. In particular, glob... more Phase-Contrast MRI (PC-MRI) is a noninvasive technique to measure blood flow. In particular, global but highly quantitative cerebral blood flow (CBF) measurement using PC-MRI complements several other CBF mapping methods such as arterial spin labeling and dynamic susceptibility contrast MRI by providing a calibration factor. The ability to estimate blood supply in physiological units also lays a foundation for assessment of brain metabolic rate. However, a major obstacle before wider applications of this method is that the slice positioning of the scan, ideally placed perpendicular to the feeding arteries, requires considerable expertise and can present a burden to the operator. In the present work, we proposed that the majority of PC-MRI scans can be positioned using an automatic algorithm, leaving only a small fraction of arteries requiring manual positioning. We implemented and evaluated an algorithm for this purpose based on feature extraction of a survey angiogram, which is of minimal operator dependence. In a comparative test-retest study with 7 subjects, the blood flow measurement using this algorithm showed an inter-session coefficient of variation (CoV) of 4:07+3:03%. The Bland-Altman method showed that the automatic method differs from the manual method by between {8% and 11%, for 95% of the CBF measurements. This is comparable to the variance in CBF measurement using manually-positioned PC MRI alone. In a further application of this algorithm to 157 consecutive subjects from typical clinical cohorts, the algorithm provided successful positioning in 89.7% of the arteries. In 79.6% of the subjects, all four arteries could be planned using the algorithm. Chi-square tests of independence showed that the success rate was not dependent on the age or gender, but the patients showed a trend of lower success rate (p = 0.14) compared to healthy controls. In conclusion, this automatic positioning algorithm could improve the application of PC-MRI in CBF quantification.
Eating disorders develop through a combination of genetic vulnerability and environmental stress,... more Eating disorders develop through a combination of genetic vulnerability and environmental stress, however the genetic basis of this risk is unknown. Methods To understand the genetic basis of this risk, we performed whole exome sequencing on 93 unrelated individuals with eating disorders (38 restricted-eating and 55 binge-eating) to identify novel damaging variants. Candidate genes with an excessive burden of predicted damaging variants were then prioritized based upon an unbiased, data-driven bioinformatic analysis. One top candidate pathway was empirically tested for therapeutic potential in a mouse model of binge-like eating. Results An excessive burden of novel damaging variants was identified in 186 genes in the restricted-eating group and 245 genes in the binge-eating group. This list is significantly enriched (OR = 4.6, p<0.0001) for genes involved in neuropeptide/neurotrophic pathways implicated in appetite regulation, including neurotensin-, glucagon-like peptide 1-and BDNF-signaling. Administration of the glucagon-like peptide 1 receptor agonist exendin-4 significantly reduced food intake in a mouse model of 'binge-like' eating. Conclusions These findings implicate ultra-rare and novel damaging variants in neuropeptide/neurotropic factor signaling pathways in the development of eating disorder behaviors and identify glucagon-like peptide 1-receptor agonists as a potential treatment for binge eating.
Anorexia nervosa and bulimia nervosa are common and severe eating disorders (EDs) of unknown etio... more Anorexia nervosa and bulimia nervosa are common and severe eating disorders (EDs) of unknown etiology. Although genetic factors have been implicated in the psychopathology of EDs, a clear biological pathway has not been delineated. DNA from two large families affected by EDs was collected, and mutations segregating with illness were identified by whole-genome sequencing following linkage mapping or by whole-exome sequencing. In the first family, analysis of twenty members across three generations identified a rare missense mutation in the estrogen-related receptor α (ESRRA) gene that segregated with illness. In the second family, analysis of eight members across four generations identified a missense mutation in the histone deacetylase 4 (HDAC4) gene that segregated with illness. ESRRA and HDAC4 were determined to interact both in vitro in HeLa cells and in vivo in mouse cortex. Transcriptional analysis revealed that HDAC4 potently represses the expression of known ESRRA-induced target genes. Biochemical analysis of candidate mutations revealed that the identified ESRRA mutation decreased its transcriptional activity, while the HDAC4 mutation increased transcriptional repression of ESRRA. Our findings suggest that mutations that result in decreased ESRRA activity increase the risk of developing EDs.
Instead, all signals appear to be multiplicatively scaled by attention. Houston, Texas 77030 The ... more Instead, all signals appear to be multiplicatively scaled by attention. Houston, Texas 77030 The effects of attention on the second aspect of neuronal responses, the noise, have not previously been studied. Spike counts of the responses of neocortical Summary neurons to stimuli that are present for several hundred milliseconds are characteristically variable (Tolhurst et To determine the physiological mechanisms underlying the enhancement of performance by attention, we al., 1981; Tomko and Crapper, 1984; Snowden et al., 1992), far more so than the responses of some peripheral examined how attention affects the ability of isolated neurons to discriminate orientation by investigating neurons (e.g., Matthews and Stein, 1969; Whitsel et al., 1977). The source of the variability is unknown. It may the reliability of responses with and without attention. Recording from 262 neurons in cortical area V4 while result from several sources, including synaptic processes, cyclical changes resulting from slow-wave ac-two rhesus macaques did a delayed match-to-sample task with oriented stimuli, we found that attention did tivity in the brain, or changes in the response characteristics of individual neurons (Tomko and Crapper, 1984; not produce detectable changes in the variability of neuronal responses but did improve the orientation Softky and Koch, 1993; Shadlen and Newsome, 1995, 1998). Some studies have suggested that lower variance discriminability of the neurons. We also found that attention did not change the relationship between is found in alert animals compared to anesthetized animals, although the effects are typically small (Vogels et burst rate and response rate. Our results are consistent with the idea that attention selects groups of neu-al., 1989; Snowden et al., 1992). The variability of responses depends in a characteris-rons for a multiplicative enhancement in response strength. tic way on response magnitude. The variance of spike counts is typically proportional to the mean number of spikes produced by a stimulus (Henry et al., 1973; Heg
We examined how attention affected the orientation tuning of 262 isolated neurons in extrastriate... more We examined how attention affected the orientation tuning of 262 isolated neurons in extrastriate area V4 and 135 neurons in area V1 of two rhesus monkeys. The animals were trained to perform a delayed match-to-sample task in which oriented stimuli were presented in the receptive field of the neuron being recorded. On some trials the animals were instructed to pay attention to those stimuli, and on other trials they were instructed to pay attention to other stimuli outside the receptive field. In this way, orientation-tuning curves could be constructed from neuronal responses collected in two behavioral states: one in which those stimuli were attended by the animal and one in which those stimuli were ignored by the animal. We fit Gaussians to the neuronal responses to twelve different orientations for each behavioral state. Although attention enhanced the responses of V4 neurons (median 26% increase) and V1 neurons (median 8% increase), selectivity, as measured by the width of its orientation-tuning curve, was not systematically altered by attention. The effects of attention were consistent with a multiplicative scaling of the driven response to all orientations. We also found that attention did not cause systematic changes in the undriven activity of the neurons.
Anorexia nervosa (AN) patients have been found to have problems in social cognition, including th... more Anorexia nervosa (AN) patients have been found to have problems in social cognition, including the process of thinking about other people&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s thoughts and feelings, often referred to as Theory of Mind (ToM). We examined neural correlates relating to thinking about social relationships in 17 women in recovery from anorexia (RAN) and 17 healthy women (CON) using a functional magnetic resonance imaging (fMRI) task. The task consisted of short videos of moving shapes that subjects viewed either in the context of performing a social decision related to how the shapes interacted: &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;People: All friends?&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; or in the context of performing a visuospatial task related to how the shapes moved after bumping into each other: &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Bumper cars: Same weight?&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;. The RAN participants showed reduced activation in the social cognition network, with the most robust differences in the right temporoparietal junction (RTPJ). There were no significant differences between the CON and RAN groups in regions more active during the visuospatial task. These neural correlates show differences in the processing of social knowledge in RAN subjects suggesting that biological impairments in social cognition may contribute to pathology in AN.
Attention is the mechanism with which we select specific aspects of our environment for processin... more Attention is the mechanism with which we select specific aspects of our environment for processing. Psychological experiments have shown that attention can be directed to a spatial location or to a particular object. Electrophysiological studies in trained macaque monkeys have found that attention can strengthen the responses of neurons in cortical area V4. Some of these studies have attributed these effects to spatial attention, whereas others have suggested that feature-directed attention may modulate the neuronal response. Here we report that neuronal correlates for both spatial and feature-directed attention exist in individual neurons in area V4 of behaving rhesus monkeys.
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